TY - JOUR
T1 - Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein specification in vertebrates
AU - Chun, Chang Z.
AU - Kaur, Sukhbir
AU - Samant, Ganesh V.
AU - Wang, Ling
AU - Pramanik, Kallal
AU - Garnaas, Maija K.
AU - Li, Keguo
AU - Field, Lyndsay
AU - Mukhopadhyay, Debabrata
AU - Ramchandranl, Ramani
PY - 2009/1/29
Y1 - 2009/1/29
N2 - In vertebrates, molecular mechanisms dictate angioblasts' migration and subsequent differentiation into arteries and veins. In this study, we used a microarray screen to identify a novel member of the sucrose nonfermenting related kinase (snrk-1) family of serine/threonine kinases expressed specifically in the embryonic zebrafish vasculature and investigated its function in vivo. Using gain-and loss-of-function studies in vivo, we show that Snrk-1 plays an essential role in the migration, maintenance, and differentiation of angioblasts. The kinase function of Snrk-1 is critical for migration and maintenance, but not for the differentiation of angioblasts. In vitro, snrk-1 knockdown endothelial cells show only defects in migration. The snrk-1 gene acts downstream or parallel to notch and upstream of gridlock during artery-vein specification, and the human gene compensates for zebrafish snrk-1 knockdown, suggesting evolutionary conservation of function.
AB - In vertebrates, molecular mechanisms dictate angioblasts' migration and subsequent differentiation into arteries and veins. In this study, we used a microarray screen to identify a novel member of the sucrose nonfermenting related kinase (snrk-1) family of serine/threonine kinases expressed specifically in the embryonic zebrafish vasculature and investigated its function in vivo. Using gain-and loss-of-function studies in vivo, we show that Snrk-1 plays an essential role in the migration, maintenance, and differentiation of angioblasts. The kinase function of Snrk-1 is critical for migration and maintenance, but not for the differentiation of angioblasts. In vitro, snrk-1 knockdown endothelial cells show only defects in migration. The snrk-1 gene acts downstream or parallel to notch and upstream of gridlock during artery-vein specification, and the human gene compensates for zebrafish snrk-1 knockdown, suggesting evolutionary conservation of function.
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U2 - 10.1182/blood-2008-06-162156
DO - 10.1182/blood-2008-06-162156
M3 - Article
C2 - 18723694
AN - SCOPUS:59649109527
SN - 0006-4971
VL - 113
SP - 1192
EP - 1199
JO - Blood
JF - Blood
IS - 5
ER -